Universität zu Köln

Shalaby, Raed, Diwan, Arzoo, Flores-Romero, Hector ORCID: 0000-0003-0996-5717, Hertlein, Vanessa and Garcia-Saez, Ana J. . Visualization of BOK pores independent of BAX and BAK reveals a similar mechanism with differing regulation. Cell Death Differ.. LONDON: SPRINGERNATURE. ISSN 1476-5403

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Abstract

BOK is a poorly understood member of the BCL-2 family of proteins that has been proposed to function as a pro-apoptotic, BAX-like effector. However, the molecular mechanism and structural properties of BOK pores remain enigmatic. Here, we show that the thermal stability and pore activity of BOK depends on the presence of its C-terminus as well as on the mitochondrial lipid cardiolipin. We directly visualized BOK pores in liposomes by electron microscopy, which appeared similar to those induced by BAX, in line with comparable oligomerization properties quantified by single molecule imaging. In addition, super-resolution STED imaging revealed that BOK organized into dots and ring-shaped assemblies in apoptotic mitochondria, also reminiscent of those found for BAX and BAK. Yet, unlike BAX and BAK, the apoptotic activity of BOK was limited by partial mitochondrial localization and was independent of and unaffected by other BCL-2 proteins. These results suggest that, while BOK activity is kept in check by subcellular localization instead of interaction with BCL-2 family members, the resulting pores are structurally similar to those of BAX and BAK. BOK-induced pores were directly visualized in liposomes using negative staining EM. BOK apoptotic activity is comparable to and independent of BAX and BAK, including formation of rings in apoptotic mitochondria. Apoptosis induction by BOK is limited by partial mitochondrial localization.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shalaby, Raed UNSPECIFIED UNSPECIFIED UNSPECIFIED Diwan, Arzoo UNSPECIFIED UNSPECIFIED UNSPECIFIED Flores-Romero, Hector UNSPECIFIED orcid.org/0000-0003-0996-5717 UNSPECIFIED Hertlein, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Saez, Ana J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-667251
DOI:	10.1038/s41418-022-01078-w
Journal or Publication Title:	Cell Death Differ.
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5403
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BCL-2 FAMILY-MEMBER; MEMBRANE-ACTIVITY; PROAPOPTOTIC BAX; MITOCHONDRIA; PROTEIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66725